ABSTRACT The University of Pittsburgh Alzheimer's Disease Research Center (PITT-ADRC) has shown a clear scientific evolution over the past three decades. Since our inception, we have advanced the areas of AD neuropsychiatry, the natural history of AD, validation of clinical criteria, and clinico-pathological correlations. We have pioneered new positron emission technology (PET) techniques for amyloid imaging. We have used a multidisciplinary approach to better understand the transition from normalcy to dementia, have explored the biology of more aggressive forms of AD characterized by psychosis, and have made and contributed to new insights in genetics. This solid scientific background has allowed the PITT-ADRC to develop areas of excellence, which will serve as the basis for the future of the Center. These are reflected in the Center's cores and projects, and most notably in the large number of studies we support in Pittsburgh and at the national and international level. Equally important, the availability of a rich, multidisciplinary training environment along with dedicated, skilled mentoring creates the ?perfect laboratory? to develop and advance young investigators. With our Projects, we are committed to remain at the forefront of the scientific efforts to understand the pathological processes involved in the etiology of AD. Project-1 takes a comprehensive neuroimaging approach to studying subjective cognitive decline (in the context of personality factors), with a focus on amyloid PET imaging as the putative earliest indicator of AD pathology. Project-2 will combine amyloid PET and a measure of synaptic density (11C- UCB-J) to examine pathological status of cognitively normal control subjects who are amyloid- negative but already show hypometabolism or hippocampal atrophy. Project 3 will examine the pathological basis of psychotic symptoms in AD patients, which have a tremendous effect on the quality of life of the patients and their families, and are risk factors for rapid clinical progression of the disease and mortality. The PITT-ADRC, through its pilot projects, engages and involves as many clinical and basic researchers as possible. This extends to all aspects of research relevant to AD and related dementias. The goal of this Revision application is to augment the acquisition of brain imaging data (both MRI and PET), standardize the analysis of all imaging data acquired from ADRC participants, and to make these data available to ADRC investigators, collaborators, and large data repositories (e.g., NACC, ENIGMA) for further analysis.